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EC number: 280-489-7 | CAS number: 83567-04-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From January 20, 1999 to February 17, 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Test material form:
- solid: particulate/powder
- Remarks:
- red powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- - Based on guidelines
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Origin: Harlan Winkelmann
Acclimatization: at least 5 d
Body weight at start for males: 280 g and for females: 209 g
Age: 5-6 weeks
Temperature and relative humidity: 22 +/-3°C and 50+/-20%, respectively
Lighting time: 12 h daily
Food: ssniff R/M-H (V 1534), ad libitum (except for the period in which the animals were kept in diuresis cages)
Water: tap water, ad libitum (except for the period in which the animals were kept in diuresis cages)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- deionized
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Determination of the solubility, stability and homogenecity of the test substance (3 samples)
- Method: HPLC-separation on a reverse phase column followed by a spectrophotometric detection (515 nm)
- Results obtained: acceptable - Duration of treatment / exposure:
- Main test group: 28 d
Recovery group: 14 d - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 62.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- On Day 29, five animals from each group were sacrificed and necropsied. The remaining animals from the control and high dose groups were sacrifiecd and necropsied after a recovery period of 14 d.
Volume administered: 5 mL/kg bw/day - Positive control:
- -
Examinations
- Observations and examinations performed and frequency:
- - Behavior and state of health were observed daily
- Body weights and food consumption were recorded twice weekly, and water consumption once weekly
- Once before the first treatment and thereafter once a week detailed clinical observations were performed in all animals outside the home cage in a standard arena (open field). Additionally, the animals were examined for opacity of the refracting media of the eyes, damage to the oral mucosa, and impairment of dental growth
- Neurotoxicological measurements including assessment of sensory function, motor activity, forelimb and hindlimb grip strength were conducted at the end of the treatment period
- Hematological examinations and clinical chemistry were carried at the end of the treatment period and after the recovery period
- Urine analysis was performed at the end of the treatment period and after the recovery period - Sacrifice and pathology:
- - During necropsy, the animals were examined for macroscopically visible abnormalities, the main organs were weighed and the organ to body weight ratios calculated. Main organs and tissues were processed for histopathological examination and checked for microscopically visible changes
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- - No systemic effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - Slightly decreased albumin values in both sexes from the high dose group and slightly decreased protein concentrations in females from the high dose group
- The serum was discolored salmon pink - Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - The urine showed a salmon pink discoloration in all animals from the high group and a very slight salmon pink discoloration in one male from the intermediate dose group
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - Kidneys were discolored red in both sexes from the intermediate and high dose group at necropsy. Additionally, light red discoloration of testes and adipose tissue was observed in the animals from the high group
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- - Mixed cellular infiltrations in the submucosa of the stomach in the animals from the intermediate and high dose group were observed, with the severity being dose-dependent
- Histopathological findings: neoplastic:
- not examined
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Remarks:
- local effects
- Effect level:
- 62.5 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: non-neoplastic
- Key result
- Dose descriptor:
- NOEL
- Remarks:
- systemic effects
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- System:
- gastrointestinal tract
- Organ:
- stomach
- Treatment related:
- yes
- Dose response relationship:
- yes
Applicant's summary and conclusion
- Conclusions:
- Under the study conditions, the NOELs of the substance for local and systemic effects in rats were determined to be 62.5 mg/kg bw/day and 250.0 mg/kg bw/day, respectively.
- Executive summary:
A study was conducted to determine the oral repeated dose toxicity of the substance according to OECD Guideline 407 and EU Method B.7, in compliance with GLP. Five Sprague-Dawley rats per sex per group were administered by oral gavage repeated dose of the substance at 0, 62.5, 250 and 1000 mg/kg bw for 28 d followed by a 14 d recovery period. The solubility, stability and homogeneity of the test formulation were analysed by HPLC and spectrophotometric methods and the results were considered acceptable. Clinical signs and mortality were observed daily. Body weights and food consumption were recorded twice weekly, and water consumption was recorded once weekly. Once before the first treatment and thereafter once a week, detailed clinical observations were performed in all animals in an open field. Additionally, the animals were examined for opacity of the eyes, damage to the oral mucosa, and impairment of dental growth. Neurotoxicological measurements including assessment of sensory function, motor activity, forelimb and hindlimb grip strength were conducted at the end of the treatment period. Hematological and clinical chemistry measurements were carried out at the end of the treatment period and after the recovery period. Urine analysis was performed at the end of the treatment period and after the recovery period. During necropsy, the animals were examined for macroscopically visible abnormalities and organ weights. Selected organs and tissues were processed for histopathological examination. No evidence of systemic toxicity was observed except for slightly decreased albumin levels in both sexes and slightly decreased protein concentrations in females from the high dose group. Microscopically, mixed cellular infiltrations in the submucosa of the stomach at the mid and high dose groups were observed, suggestive of localised irritation in the stomach. Under the study conditions, the NOELs of the substance for local and systemic effects in rats were determined to be 62.5 mg/kg bw/day and 250.0 mg/kg bw/day, respectively (Hofmann, 1999).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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